Haczku A, Macary P, Huang T J, Tsukagoshi H, Barnes P J, Kay A B, Kemeny D M, Chung K F, Moqbel R
Department of Allergy and Clinical Immunology, Guy's Hospital, London, UK.
Immunology. 1997 Jun;91(2):176-85. doi: 10.1046/j.1365-2567.1997.d01-2221.x.
Following allergen exposure, sensitized Brown-Norway rats develop airway hyperresponsiveness (AHR) and eosinophilic inflammation together with an increase in activated T cells (CD25+) in the airways. We tested the hypothesis that CD4+ T cells are involved directly in the acquisition of AHR. Spleen T cells from animals that were injected intraperitoneally on three consecutive days with ovalbumin/Al(OH)3, showed a dose-dependent proliferative response in vitro to ovalbumin, but not to bovine serum albumin, as measured by [3H]thymidine uptake. For total T-cell transfer, spleen cells obtained from donor rats 4 days after sensitization were depleted of adherent cells by a nylon wool column separation. CD4+ and CD8+ T cells were purified by immunomagnetic beads cell separation. Recipient naive rats were injected intravenously with 50 x 10(6) total T cells, 20 x 10(6) and 5 x 10(6) CD4+ cells, and 5 x 10(6) CD8+ cells, and were exposed to ovalbumin aerosol 24 hr afterwards. After a further 24 hr, airway responsiveness to acetylcholine (ACh) was measured and provocative concentration (PC) values PC100, PC200 and PC300) (the ACh concentration needed to achieve 100, 200 and 300% increase in lung resistance above baseline) were calculated. Airway responsiveness was significantly increased in recipients of sensitized total T cells compared with recipients of cells from saline-injected donor rats (P < 0.05). There were significantly increased eosinophil major basic protein (MBP)+ cell counts/mm2 in airway submucosal tissue in the hyperreactive rats and a significant correlation was found between the number of MBP+ cells and PC100 (r = 0.75; P < 0.03) in recipients of sensitized total T cells. Purified CD4+ T cells from sensitized donors induced AHR in naive recipients (P < 0.05), while sensitized CD8+ and naive CD4+ cells failed to do so. Our data indicate that T cells may induce AHR through an eosinophilic airway inflammation and that CD4+ T cells may have a direct effect in this process in Brown-Norway rats.
暴露于变应原后，致敏的棕色挪威大鼠会出现气道高反应性（AHR）、嗜酸性粒细胞炎症，同时气道中活化T细胞（CD25+）数量增加。我们检验了CD4+ T细胞直接参与AHR形成的假说。连续三天腹腔注射卵清蛋白/氢氧化铝的动物的脾T细胞，通过[3H]胸腺嘧啶核苷摄取检测，在体外对卵清蛋白呈现剂量依赖性增殖反应，但对牛血清白蛋白无反应。对于全T细胞转移，致敏4天后从供体大鼠获取的脾细胞通过尼龙毛柱分离去除黏附细胞。通过免疫磁珠细胞分离纯化CD4+和CD8+ T细胞。受体新生大鼠静脉注射5×10⁶个全T细胞、2×10⁶个和5×10⁶个CD4+细胞以及5×10⁶个CD8+细胞，24小时后暴露于卵清蛋白气雾剂。再过24小时后，测量气道对乙酰胆碱（ACh）的反应性，并计算激发浓度（PC）值PC100、PC200和PC300（使肺阻力比基线增加100%、200%和300%所需的ACh浓度）。与注射生理盐水的供体大鼠的细胞受体相比，致敏全T细胞受体的气道反应性显著增加（P<0.05）。高反应性大鼠气道黏膜下组织中嗜酸性粒细胞主要碱性蛋白（MBP）+细胞计数/mm²显著增加，在致敏全T细胞受体中，MBP+细胞数量与PC100之间存在显著相关性（r = 0.75；P<0.03）。来自致敏供体的纯化CD4+ T细胞在新生受体中诱导了AHR（P<0.05），而致敏CD8+和新生CD4+细胞则未能诱导。我们的数据表明，T细胞可能通过嗜酸性粒细胞气道炎症诱导AHR，并且在棕色挪威大鼠中，CD4+ T细胞可能在此过程中具有直接作用。
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